CN117797105A - Oxcarbazepine chewable tablet and preparation method thereof - Google Patents
Oxcarbazepine chewable tablet and preparation method thereof Download PDFInfo
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- CN117797105A CN117797105A CN202311823426.2A CN202311823426A CN117797105A CN 117797105 A CN117797105 A CN 117797105A CN 202311823426 A CN202311823426 A CN 202311823426A CN 117797105 A CN117797105 A CN 117797105A
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- oxcarbazepine
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- 229960001816 oxcarbazepine Drugs 0.000 title claims abstract description 63
- CTRLABGOLIVAIY-UHFFFAOYSA-N oxcarbazepine Chemical compound C1C(=O)C2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 CTRLABGOLIVAIY-UHFFFAOYSA-N 0.000 title claims abstract description 63
- 239000007910 chewable tablet Substances 0.000 title claims abstract description 46
- 229940068682 chewable tablet Drugs 0.000 title claims abstract description 42
- 238000002360 preparation method Methods 0.000 title claims abstract description 10
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 14
- 239000000945 filler Substances 0.000 claims abstract description 12
- 239000000796 flavoring agent Substances 0.000 claims abstract description 10
- 235000013355 food flavoring agent Nutrition 0.000 claims abstract description 10
- 239000000314 lubricant Substances 0.000 claims abstract description 10
- 239000000853 adhesive Substances 0.000 claims abstract description 8
- 230000001070 adhesive effect Effects 0.000 claims abstract description 8
- 238000002156 mixing Methods 0.000 claims description 25
- 239000000463 material Substances 0.000 claims description 18
- 239000002245 particle Substances 0.000 claims description 16
- 238000005550 wet granulation Methods 0.000 claims description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 14
- 239000008187 granular material Substances 0.000 claims description 13
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 10
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 9
- 238000007908 dry granulation Methods 0.000 claims description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 8
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 7
- 238000001035 drying Methods 0.000 claims description 7
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 7
- 238000003756 stirring Methods 0.000 claims description 7
- 229940075614 colloidal silicon dioxide Drugs 0.000 claims description 6
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 6
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 6
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 6
- 229960003943 hypromellose Drugs 0.000 claims description 6
- 238000010008 shearing Methods 0.000 claims description 6
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 5
- 229930195725 Mannitol Natural products 0.000 claims description 5
- 239000004376 Sucralose Substances 0.000 claims description 5
- 239000007884 disintegrant Substances 0.000 claims description 5
- 235000019359 magnesium stearate Nutrition 0.000 claims description 5
- 239000000594 mannitol Substances 0.000 claims description 5
- 235000010355 mannitol Nutrition 0.000 claims description 5
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 5
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 5
- 229940069328 povidone Drugs 0.000 claims description 5
- 235000019408 sucralose Nutrition 0.000 claims description 5
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 claims description 5
- 229920002472 Starch Polymers 0.000 claims description 4
- 229960000913 crospovidone Drugs 0.000 claims description 4
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims description 4
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims description 4
- 239000011734 sodium Substances 0.000 claims description 4
- 229910052708 sodium Inorganic materials 0.000 claims description 4
- 239000008107 starch Substances 0.000 claims description 4
- 235000019698 starch Nutrition 0.000 claims description 4
- 108010011485 Aspartame Proteins 0.000 claims description 3
- 229920002785 Croscarmellose sodium Polymers 0.000 claims description 3
- 235000021355 Stearic acid Nutrition 0.000 claims description 3
- 229930006000 Sucrose Natural products 0.000 claims description 3
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 3
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 3
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 claims description 3
- 239000000605 aspartame Substances 0.000 claims description 3
- 235000010357 aspartame Nutrition 0.000 claims description 3
- 229960003438 aspartame Drugs 0.000 claims description 3
- 239000011230 binding agent Substances 0.000 claims description 3
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 claims description 3
- 235000013539 calcium stearate Nutrition 0.000 claims description 3
- 239000008116 calcium stearate Substances 0.000 claims description 3
- 229960001681 croscarmellose sodium Drugs 0.000 claims description 3
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims description 3
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 claims description 3
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 3
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 3
- 229940083542 sodium Drugs 0.000 claims description 3
- 235000015424 sodium Nutrition 0.000 claims description 3
- 229940045902 sodium stearyl fumarate Drugs 0.000 claims description 3
- 239000008117 stearic acid Substances 0.000 claims description 3
- 239000005720 sucrose Substances 0.000 claims description 3
- 229950005770 hyprolose Drugs 0.000 claims description 2
- 239000011148 porous material Substances 0.000 claims description 2
- 239000000454 talc Substances 0.000 claims description 2
- 235000012222 talc Nutrition 0.000 claims description 2
- 229910052623 talc Inorganic materials 0.000 claims description 2
- 238000000034 method Methods 0.000 claims 2
- 239000003826 tablet Substances 0.000 abstract description 18
- 239000003814 drug Substances 0.000 abstract description 17
- 229940079593 drug Drugs 0.000 abstract description 8
- 210000000214 mouth Anatomy 0.000 abstract description 4
- 230000000694 effects Effects 0.000 abstract description 2
- 238000004090 dissolution Methods 0.000 description 6
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 5
- 208000019505 Deglutition disease Diseases 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 4
- 238000010828 elution Methods 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 239000001961 anticonvulsive agent Substances 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 230000029087 digestion Effects 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 229910001220 stainless steel Inorganic materials 0.000 description 3
- 239000010935 stainless steel Substances 0.000 description 3
- 229960003965 antiepileptics Drugs 0.000 description 2
- 230000001055 chewing effect Effects 0.000 description 2
- 238000007922 dissolution test Methods 0.000 description 2
- 238000004811 liquid chromatography Methods 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- FFGPTBGBLSHEPO-UHFFFAOYSA-N carbamazepine Chemical class C1=CC2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 FFGPTBGBLSHEPO-UHFFFAOYSA-N 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
- 238000007599 discharging Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000007661 gastrointestinal function Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 description 1
- 238000005453 pelletization Methods 0.000 description 1
- 239000008055 phosphate buffer solution Substances 0.000 description 1
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 238000004513 sizing Methods 0.000 description 1
- DAJSVUQLFFJUSX-UHFFFAOYSA-M sodium;dodecane-1-sulfonate Chemical compound [Na+].CCCCCCCCCCCCS([O-])(=O)=O DAJSVUQLFFJUSX-UHFFFAOYSA-M 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 235000020985 whole grains Nutrition 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to the technical field of biological medicines, and particularly relates to an oxcarbazepine chewable tablet and a preparation method thereof. The oxcarbazepine chewable tablet provided by the invention comprises the following components in percentage by mass: 65 to 85 percent of oxcarbazepine, 6.5 to 20 percent of filler, 1 to 3 percent of adhesive, 4 to 7 percent of disintegrating agent, 1 to 2 percent of flavoring agent, 0.5 to 1.5 percent of glidant and 1 to 1.5 percent of lubricant. The oxcarbazepine chewable tablet provided by the invention can be directly chewed and taken in the oral cavity, has good taste and high patient adaptability; and the medicine has the same medicine release behavior and curative effect as the existing oxcarbazepine tablet.
Description
Technical Field
The invention belongs to the technical field of biological medicines, and particularly relates to an oxcarbazepine chewable tablet and a preparation method thereof.
Background
Oxcarbazepine is a second generation antiepileptic drug and is a derivative of carbamazepine which is a first generation antiepileptic drug. The medicine mainly acts through its pharmacologically active metabolite (10-monohydroxy derivative, MHD). The oxcarbazepine preparation is mainly tablets and suspension, and the tablets are the main dosage forms in the market at present due to the problem of inconvenient carrying of the suspension. The single drug for treating adults is used for treating the adult, and the daily maintenance dose range is 600-2400 mg. The tablet weight of the single 300mg standard tablet is about 420mg, the daily dosage of the existing oxcarbazepine tablet is larger, and more time and effort are needed for dysphagia patients to convey the medicine from the oral cavity into the stomach. Larger sized tablets may also cause medication pain. The dysphagia of the existing oxcarbazepine tablet may occur at any age, and the problem of poor clinical adaptability of patients exists.
Disclosure of Invention
In view of the above, the invention provides an oxcarbazepine chewable tablet and a preparation method thereof, and the oxcarbazepine chewable tablet provided by the invention is convenient for patients to take and carry, and improves the medication compliance of patients.
In order to solve the technical problems, the invention provides an oxcarbazepine chewable tablet which comprises the following components in percentage by mass:
preferably, the filler comprises mannitol or sucrose.
Preferably, the binder comprises hypromellose, povidone, or hyprolose.
Preferably, the disintegrant comprises crospovidone, croscarmellose sodium or sodium carboxymethyl starch.
Preferably, the flavoring agent comprises sucralose, or aspartame.
Preferably, the glidant comprises colloidal silicon dioxide or talcum powder;
the lubricant includes magnesium stearate, calcium stearate, sodium stearyl fumarate or stearic acid.
Preferably, the oxcarbazepine chewable tablet further comprises essence, wherein the mass percentage of the essence in the oxcarbazepine chewable tablet is 0.18-0.22%.
The invention also provides a preparation method of the oxcarbazepine chewable tablet, which comprises the following steps:
mixing oxcarbazepine, a filler, an adhesive, a part of disintegrating agent and a part of glidant to obtain a mixed material;
mixing the mixed material with water, and performing wet granulation to obtain wet granules;
mixing the wet granules after drying with the residual disintegrating agent, the residual glidant and the flavoring agent, carrying out dry granulation, and taking undersize to obtain dry granules;
and mixing the dry particles with a lubricant, and tabletting to obtain the oxcarbazepine chewable tablet.
Preferably, the mass ratio of the water to the mixed material is 15-25:100;
the stirring rotation speed of the wet granulation is 100-140 rpm, and the shearing rotation speed is 450-550 rpm; the wet granulation time is 1-3 min.
Preferably, the aperture of the screen for dry granulation is 1.5mm;
the bulk density of the dry particles is 0.4-0.6 g/mL, and the D60 of the dry particles is 180-230 mu m.
The invention provides an oxcarbazepine chewable tablet which comprises the following components in percentage by mass: 65 to 85 percent of oxcarbazepine, 6.5 to 20 percent of filler, 1 to 3 percent of adhesive, 4 to 7 percent of disintegrating agent, 1 to 2 percent of flavoring agent, 0.5 to 1.5 percent of glidant and 1 to 1.5 percent of lubricant. The oxcarbazepine chewable tablet provided by the invention can be directly chewed and taken in the oral cavity, has good taste and high patient adaptability; and the medicine has the same medicine release behavior and curative effect as the existing oxcarbazepine tablet.
Detailed Description
The invention provides an oxcarbazepine chewable tablet which comprises the following components in percentage by mass:
in the present invention, all materials are conventional commercial products unless otherwise specified.
The oxcarbazepine chewable tablet provided by the invention comprises 65-85% of oxcarbazepine, preferably 70-75% by mass.
The oxcarbazepine chewable tablet provided by the invention comprises 6.5-20% of filler, preferably 13.4-15.6%, and more preferably 13.6% by mass. In the present invention, the filler preferably includes mannitol or sucrose, more preferably mannitol.
The oxcarbazepine chewable tablet provided by the invention comprises 1-3% of adhesive, preferably 2.2-2.5% by mass. In the present invention, the binder preferably includes hypromellose, povidone, or hypromellose, more preferably hypromellose. In the present invention, the weight average molecular weight of the hydroxypropylcellulose is preferably 80000 to 95000, more preferably 95000; the type of the hydroxypropyl cellulose is preferably hydroxypropyl cellulose LF or hydroxypropyl cellulose EF, and more preferably hydroxypropyl cellulose LF.
The oxcarbazepine chewable tablet provided by the invention comprises 4-7% of disintegrating agent, preferably 4-6% by mass. In the present invention, the disintegrant preferably includes crospovidone, croscarmellose sodium or sodium carboxymethyl starch, more preferably crospovidone or sodium carboxymethyl starch.
The oxcarbazepine chewable tablet provided by the invention comprises 1-2% of flavoring agent, preferably 1.5-1.8% by mass. In the present invention, the flavoring agent preferably comprises sucralose or aspartame, more preferably sucralose.
The oxcarbazepine chewable tablet provided by the invention comprises 0.5-1.5% of glidant, preferably 0.7-1.2% by mass. In the present invention, the glidant preferably comprises colloidal silicon dioxide, or talc, more preferably colloidal silicon dioxide.
The oxcarbazepine chewable tablet provided by the invention comprises 1-1.5% of lubricant, preferably 1.1-1.3% by mass. In the present invention, the lubricant preferably includes magnesium stearate, calcium stearate, sodium stearyl fumarate or stearic acid, more preferably magnesium stearate.
In the invention, the oxcarbazepine chewable tablet preferably further comprises essence, wherein the mass percentage of the essence in the oxcarbazepine chewable tablet is preferably 0.18-0.22%, more preferably 0.2%. In the present invention, the essence is preferably orange powder essence.
The invention also provides a preparation method of the oxcarbazepine chewable tablet, which comprises the following steps:
mixing oxcarbazepine, a filler, an adhesive, a part of disintegrating agent and a part of glidant to obtain a mixed material;
mixing the mixed material with water, and performing wet granulation to obtain wet granules;
mixing the wet granules after drying with the residual disintegrating agent, the residual glidant and the flavoring agent, carrying out dry granulation, and taking undersize to obtain dry granules;
and mixing the dry particles with a lubricant, and tabletting to obtain the oxcarbazepine chewable tablet.
Oxcarbazepine, a filler, an adhesive, a part of disintegrating agent and a part of glidant are mixed to obtain a mixed material. In the present invention, the content of the partial disintegrant is preferably 40 to 60% by mass, more preferably 50% by mass based on the total amount of the disintegrant. In the present invention, the content of the partial glidant is preferably 30 to 50% by mass, more preferably 40% by mass of the total glidant. In the present invention, the mixing is preferably performed in a lift hopper mixer.
After the mixed material is obtained, the wet granulation is carried out after the mixed material is mixed with water, so as to obtain wet granules. In the present invention, the mixing step preferably further comprises: putting the mixed material into a dry granulator for dispersion treatment; and (3) passing the material after the dispersion treatment through a square hole screen mesh of 2 x 2mm, and taking undersize. The invention can improve the uniformity of mixing oxcarbazepine, filler, adhesive, partial disintegrating agent and partial glidant after dispersion treatment.
In the present invention, the wet granulation process preferably further comprises: the mixture was placed in a wet granulator for mixing. In the present invention, the stirring speed of the mixing is 222 to 262rpm, more preferably 230 to 242rpm; the shearing speed of the mixing is preferably 900-1100 rpm, more preferably 950-1000 rpm; the mixing time is preferably 4 to 6 minutes, more preferably 5 minutes.
In the present invention, the water is preferably pure water. In the invention, the mass ratio of the water to the mixture is preferably 15-25:100, more preferably 18-22:100. The present invention preferably adds water to the pelletization kettle through a spray head. In the present invention, the stirring rotation speed of the wet granulation is preferably 100 to 140rpm, more preferably 110 to 120rpm; the shearing rotation speed of the wet granulation is preferably 450-550 rpm, more preferably 500-520 rpm; the wet granulation time is preferably 1 to 3 minutes, more preferably 2 minutes.
In the present invention, the wet granulation preferably further comprises: wet granulation is carried out on the wet granulated product to obtain wet granules. In the present invention, the wet-sizing screen is preferably a square-hole screen, and the square-hole side length of the square-hole screen is preferably 2×2mm.
After wet particles are obtained, the wet particles are dried, and then are mixed with the residual disintegrating agent, the residual glidant and the flavoring agent for dry granulation, and the undersize is taken to obtain dry particles. In the present invention, the drying is preferably performed in a fluidized bed; the inlet air temperature for drying is preferably 55-75 ℃, more preferably 65-70 ℃; the air quantity of the drying is preferably 500-1000 m 3 Preferably 600 to 800m 3 And/h. In the present invention, the water content of the dried product is preferably less than 1.5%, more preferably 0.5 to 1%. In the present invention, the temperature of the dried product is preferably 40 to 50 ℃, more preferably 40 to 45 ℃.
In the present invention, the mixing is preferably performed in a lift hopper mixer. In the present invention, when the oxcarbazepine chewable tablet contains essence, the wet granules are preferably mixed with the residual disintegrating agent, the residual glidant, the flavoring agent and the essence after being dried.
In the present invention, the screen for dry granulation is preferably a stainless steel screen having a circular mesh, and the screen for dry granulation preferably has a pore size of 1.5mm. In the present invention, the bulk density of the dry particles is preferably 0.4 to 0.6g/mL, more preferably 0.5g/mL; the D60 of the dry particles is preferably 180 to 230. Mu.m, more preferably 200 to 220. Mu.m.
After the dry particles are obtained, the invention mixes the dry particles with the lubricant and then tabletting the mixture to obtain the oxcarbazepine chewable tablet. In the present invention, the mixing is preferably performed in a lift hopper mixer, and the mixing time is preferably 5 to 10 minutes, more preferably 6 to 8 minutes. The invention has no special requirement on the tabletting and can be realized by adopting a conventional mode in the field. In the present invention, the hardness of the oxcarbazepine chewable tablet is preferably 120 to 160N, more preferably 130 to 150N.
The technical solutions provided by the present invention are described in detail below in conjunction with examples for further illustrating the present invention, but they should not be construed as limiting the scope of the present invention.
Example 1
300mg of oxcarbazepine, 54.4mg of mannitol, 8.4mg of hypromellose, 1.2mg of partial colloidal silicon dioxide and 12mg of partial crosslinked povidone are placed into a lifting hopper mixer to be mixed, so as to obtain a mixed material;
putting the mixed material into a dry granulator for dispersion treatment, then passing through a square hole screen with square hole size of 2 x 2mm, putting the undersize into a wet mixing granulator, carrying out premixing mixing under the condition that the stirring speed is 242rpm and the shearing speed is 1000rpm, starting a stirring paddle and a shredding knife, adding 72mg of purified water into a granulating pot through a spray head, and carrying out wet granulation for 3min under the condition that the stirring speed is 120rpm and the shearing speed is 500 rpm; wet finishing the wet granulated product by using a stainless steel square hole screen with square hole size of 2 x 2mm, and taking undersize to obtain wet granules;
transferring the wet whole grains into a fluidized bed for drying (inlet air temperature is 70 ℃ and inlet air quantity is 800 m) 3 And/h), when the water content of the dried product is 1.1%, after discharging, placing the dried product, 12mg of residual crosslinked povidone, 1.6mg of residual colloidal silicon dioxide and 6mg of sucralose in a lifting hopper mixer for premixing; carrying out dry granulation on the mixed material by utilizing a circular stainless steel screen with a screen mesh aperture of 1.5mm, and taking screen underflows to obtain dry particles (bulk density is 0.4-0.6 g/mL, D60 is 210-250 mu m);
and (3) placing the dry particles and 4.4mg of magnesium stearate into a lifting hopper mixer to complete total mixing for 8min, and tabletting to obtain the oxcarbazepine chewable tablets (with the hardness of 60-80N).
Examples 2 to 3
Oxcarbazepine chewable tablets were prepared as in example 1, except that table 1 was referenced.
Table 1 examples 1 to 3 amounts of materials
Comparative example 1
Oxcarbazepine tablets having a registration number of national drug standard HJ20171033, trade name (chinese) Qu Lai, manufacturer Novartis far s.p.a, lot number TRT36 were used as comparative examples.
The in vitro dissolution test was performed using a dissolution apparatus to simulate the release of the agents of comparative example 1 and examples 1 to 3 in vivo, and the media and conditions for dissolution are shown in Table 2.
TABLE 2 Medium and conditions for in vitro dissolution test
Note that: SDS in Table 2 is sodium dodecyl sulfonate.
The elution amounts were calculated by using the oxcarbazepine content in the liquid chromatography detection system at the time points of elution of 0min, 5min, 10min, 15min, 20min, 30min, 45min and 60min, respectively, and the results are shown in tables 3 to 5.
Conditions for liquid chromatography detection: chromatographic column with octadecylsilane chemically bonded silica as filler; taking 0.02mol/L potassium dihydrogen phosphate buffer solution as a mobile phase A and acetonitrile as a mobile phase B; the flow rate is 1.0mL/min; the column temperature is 35 ℃; the detection wavelength is 230nm; run time 15.5min; the sample volume was 10. Mu.L.
TABLE 3 Performance parameters of digestion in Medium with pH 1.0+0.5% SDS
TABLE 4 Performance parameters of digestion in Medium with pH 4.0+0.4% SDS
TABLE 5 Performance parameters of digestion in Medium with pH 6.8+0.4% SDS
F in tables 3 to 5 2 Is a dissolution fit comparison of examples 1-3 with a reference, f 2 Greater than 50 indicates similarity. Using a similarity factor (f 2 ) When the similarity of the elution profiles is compared, in general, when two elution profile similarity factors (f 2 ) When the value is not less than 50, the dissolution profile is considered to be similar.
From the data in tables 3-5, it can be seen that the oxcarbazepine chewable tablets provided by the invention can achieve similar dissolution performance in vitro as conventional commercial oxcarbazepine tablet formulations, and have a better administration mode. Conventional commercial oxcarbazepine tablets can only be taken by swallowing, for use alone or in combination with other antiepileptic drugs, suitable populations are adults and children aged 5 and above; the tablet weight is 400mg, and the daily maintenance dosage range is between 2 and 6 tablets, which belongs to long-term administration. Such large and numerous tablets need to be swallowed daily for dysphagia patients, requiring more time and effort to deliver the drug from the mouth into the stomach. Larger sized tablets may also cause medication pain. The children aged 5 years and older can have great conflict when taking the medicine in the way, which is not beneficial to clinical treatment. The oxcarbazepine chewable tablet provided by the invention can perfectly solve the problems: the chewable tablet A is convenient to take, is not limited by time and place, can be used on time even under the condition of water deficiency, is particularly suitable for children, dysphagia or patients with poor gastrointestinal functions, and can reduce the burden of the medicine on the gastrointestinal tract; the chewable tablet has good taste, so that children are not afraid of taking the tablet any more, and the compliance is good; the surface area of the chewing tablet is increased after the chewing tablet is chewed, and the dissolution and absorption of the medicine in the body are promoted.
Although the foregoing embodiments have been described in some, but not all, embodiments of the invention, it should be understood that other embodiments may be devised in accordance with the present embodiments without departing from the spirit and scope of the invention.
Claims (10)
1. The oxcarbazepine chewable tablet is characterized by comprising the following components in percentage by mass:
2. oxcarbazepine chewable tablet according to claim 1, wherein the filler comprises mannitol or sucrose.
3. Oxcarbazepine chewable tablet according to claim 1, wherein the binder comprises hypromellose, povidone or hyprolose.
4. Oxcarbazepine chewable tablet according to claim 1, wherein the disintegrant comprises crospovidone, croscarmellose sodium or sodium carboxymethyl starch.
5. The oxcarbazepine chewable tablet according to claim 1, wherein the flavoring comprises sucralose, or aspartame.
6. The oxcarbazepine chewable tablet according to claim 1, wherein the glidant comprises colloidal silicon dioxide or talc;
the lubricant includes magnesium stearate, calcium stearate, sodium stearyl fumarate or stearic acid.
7. The oxcarbazepine chewable tablet according to claim 1, further comprising essence, wherein the mass percentage of the essence in the oxcarbazepine chewable tablet is 0.18-0.22%.
8. A process for the preparation of oxcarbazepine chewable tablets according to any one of claims 1 to 7 comprising the steps of:
mixing oxcarbazepine, a filler, an adhesive, a part of disintegrating agent and a part of glidant to obtain a mixed material;
mixing the mixed material with water, and performing wet granulation to obtain wet granules;
mixing the wet granules after drying with the residual disintegrating agent, the residual glidant and the flavoring agent, carrying out dry granulation, and taking undersize to obtain dry granules;
and mixing the dry particles with a lubricant, and tabletting to obtain the oxcarbazepine chewable tablet.
9. The preparation method according to claim 8, wherein the mass ratio of the water to the mixed material is 15-25:100;
the stirring rotation speed of the wet granulation is 100-140 rpm, and the shearing rotation speed is 450-550 rpm; the wet granulation time is 1-3 min.
10. The method according to claim 8, wherein the pore size of the screen for dry granulation is 1.5mm;
the bulk density of the dry particles is 0.4-0.6 g/mL, and the D60 of the dry particles is 180-230 mu m.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311823426.2A CN117797105A (en) | 2023-12-27 | 2023-12-27 | Oxcarbazepine chewable tablet and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311823426.2A CN117797105A (en) | 2023-12-27 | 2023-12-27 | Oxcarbazepine chewable tablet and preparation method thereof |
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| CN117797105A true CN117797105A (en) | 2024-04-02 |
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| CN202311823426.2A Pending CN117797105A (en) | 2023-12-27 | 2023-12-27 | Oxcarbazepine chewable tablet and preparation method thereof |
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| Country | Link |
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| CN (1) | CN117797105A (en) |
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2023
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